Metastatic Pancreatic Ductal Adenocarcinoma (PDAC), Pancreatic Ductal Adenocarcinoma (mPDAC)
Conditions
Keywords
Hyperthermia, Medical device
Brief summary
Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and limited treatment options following failure of first-line therapy. Whole-body hyperthermia (WBHT) is a non-invasive treatment approach that raises the body's core temperature under controlled conditions and may enhance the effects of anticancer therapies through multiple biological mechanisms, including improved drug delivery, modulation of the immune response, and increased sensitivity to treatment. The MATTERS-2 study is a multicentre, randomized clinical trial designed to evaluate the efficacy and safety of WBHT in combination with standard systemic anticancer therapy in patients with metastatic PDAC after failure of first-line treatment. Participants will receive either standard systemic therapy alone or standard systemic therapy combined with WBHT. The primary objective of the study is to determine whether the addition of WBHT improves clinical outcomes compared with standard therapy alone in terms of overall survival (OS) while maintaining safety. Secondary objectives include other clinical outcomes such as progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR). Further, quality of life assessments (QoL) and exploratory biomarker analyses will also be performed.
Interventions
DEVICEWhole-body hyperthermia
Initially every 2 weeks, until a total of 3 treatments is reached. Thereafter every 4 weeks. The treatment will raise the body temperature to 41,50 °C for a total of 4 hours.
Standard-of-care systemic therapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC, stage IV) after failure of first-line treatment.
Sponsors
ElmediX
Xper research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be randomised to one of two groups: A control group with standard-of-care systemic therapy or a treatment group where WBHT is added to this standard-of-care.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects at least 18 years of age at time of signing the informed consent 2. Subjects with metastatic pancreatic adenocarcinoma (PDAC) confirmed by histology 3. Measurable disease per RECIST 1.1 4. Subjects previously treated with chemotherapy in first line for metastatic disease 5. ECOG performance status ≤ 1 6. Height ≤ 2,00 m, BMI maximal 40 or positive fitting session 7. Adequate liver structure (accessible metastasis-free and functional liver parenchyma) allowing stable liver sensor positioning without unacceptable risks of bleeding and perforation, based on echographic assessment (or any imaging modality) 8. Adequate bone marrow function defined as 1. white blood cell count ≥ 2000/µl 2. neutrophils ≥ 1500 cells/μL 3. platelets ≥ 100 x 109/L 4. hemoglobin ≥ 9 g/dl (female) and ≥10 g/dl (male) documented 9. Adequate coagulation defined as 1. PT (%) ≥ 70% 2. aPTT ≤ ULN 10. Adequate liver function defined as 1. Transaminases (AST, ALT) ≤ 2.5 x ULN or ≤ 5.0 in presence of liver metastasis 2. bilirubin ≤ 2 x ULN 11. Adequate renal function defined as calculated eGFR ≥ 60 mL/min (CKD-EPI equation) 12. Normal ionogram 13. Effective contraception for both male and female subjects if applicable. Women of childbearing potential must have a negative pregnancy test at screening visit. 14. Written informed consent must be given according to good clinical practice and national/local regulations.
Exclusion criteria
1. Pregnant or breastfeeding women 2. Presence of brain metastasis (known or suspected) 3. Other malignant diseases in the medical history during the last 5 years (exceptions: carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin) 4. Serious medical risk factors involving any of the major organ systems, including high cardiovascular risk defined as recent major cardiovascular events (such as myocardial infarction or stroke), clinically relevant heart failure due to structural or mechanical cardiac abnormalities (e.g., valvular disease or myocardial dysfunction), and clinically significant arrhythmias. 5. Pathology that would interfere with the placement of the bladder catheter 6. Clinically significant pulmonary disease which might interfere with mechanical ventilation 7. History of autonomic dysfunction (due to the influence on skin blood flow) 8. History of malignant hyperthermia 9. History of untreated endocrine pathology (e.g. diabetes type II, hyper- or hypothyroidism). 10. Primary untreated diabetes type I not related to the oncological condition (due to vascular complications). 11. Known allergies to drugs that will be used during the trial (e.g. anesthetic, analgesic, chemotherapy) 12. Active infections not controlled by medication 13. Presence of clinically significant ascites and/or decompensated cirrhosis/portal hypertension 14. Severe, non-healing wounds, ulcers or bone fractures 15. Organ allografts requiring immunosuppressive therapy 16. Implants that are not compatible with temperature changes 17. (History of) clinically significant (investigator decision) psychiatric disorder and/or psychosocial disorder that may interfere with adequate compliance to the protocol or signature of the informed consent 18. Other clinically significant disease which could impair the subject's ability to participate in the study according to the investigator's opinion 19. Participation in another clinical trial 2 weeks prior to the randomization 20. Biological therapy during the 2 weeks prior to the randomization 21. Radiotherapy up to 2 weeks prior to the randomization 22. Major surgery up to 6 weeks prior to the randomization (port-a-cath placement is minor)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | From randomization until death from any cause, assessed up to study completion (primary analysis triggered upon occurrence of 66 death events), an (expected) average of 12 months | To compare Overall Survival (OS) between WBHT + standard-of-care (SoC) and SoC treatment group |
| Safety and tolerability of WBHT + SoC and SoC alone | From moment of enrollment (ICF signature) up to End of Treatment visit, an (expected) average of 10 months | Incidence of Adverse Events (AE), Serious Adverse Events (SAE), treatment-related AE/SAE and Adverse Device Effects (ADE). They will be reported from moment of enrollment (ICF signature) up to End of Treatment visit and will be assessed for seriousness, severity and relationship to the device and to WBHT treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Up to time of progression, death or study discontinuation; an (expected) average of 8 months | To compare Progression-Free Survival (PFS) between WBHT +SoC and SoC treatment group based on RECIST 1.1. criteria. |
| Disease control rate (DCR) | Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months | To compare Disease Control Rate (DCR) between WBHT +SoC and SoC treatment group based on RECIST 1.1 criteria. |
| Objective response rate (ORR) | Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months | To compare Objective Response Rate (ORR) between WBHT +SoC and SoC treatment group based on RECIST 1.1 criteria and further described with duration of response (DOR) and time to response (TTR). |
| Quality of Life assessments (EORTC-QLQ-C30 version 3) | Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months | Quality of Life (QoL) according to EORTC-QLQ-C30 version 3 scoring changes from baseline (at 4-weeks, 8-weeks and End of Treatment) |
| Quality of Life assessments (QLQ Pan 26) | Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months | Quality of Life (QoL) according to QLQ Pan 26 scoring changes from baseline (at 4-weeks, 8-weeks and End of Treatment) |
| Evolution of CA19-9 | Until death, end of treatment visit or study discontinuation; an (expected) average of 10 months | To evaluate CA19-9 changes from baseline in WBHT +SoC and SoC treatment groups (at 4-weeks, 8-weeks and End of Treatment) |
Countries
Belgium, Spain
Contacts
CONTACTJohn-Paul Bogers, Prof. Dr.
Outcome results
None listed